The combination of outstanding chemical and physical properties of polyurethanes (PU's) coupled with their biocompatibility have led to their use in a wide range of biomedical applications. Recent studies have demonstrated the relative lack of in vivo biostability of polyether PU's. In an attempt to improve biostability, alternative PU's have been proposed for biomedical applications. Current studies in our laboratory, directed toward a fundamental understanding of biocompatibility and biostability of PU elastomers, have led to a hypothesis for the cell/polymer feedback control mechanism of in vivo biodegradation. To confirm and/or modify this hypothesis, studies will be carried out on PU's of known composition with and without specific modifications and additives that have been developed to increase the biostability of the PU. The specific aims of the proposed research are: 1. To elucidate the chemical mechanisms by which cellular degrading agents (radicals, HOCl, acid) cause hydrolytic and/or oxidative chain cleavage of polyetherurethanes, polycarbonate urethanes and other PU's with non-polyether soft segments or surface modifying endgroups, (SME's) where the mechanism(s) of biodegradation may be different. Correlative studies will be made with in vitro conditions that mimic the in vivo environment. 2. To characterize the surface degradation of PU's after in vivo and in vitro exposure, and correlate the results with the effect on performance properties. Methods of material characterization will include contact angle, X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), Fourier transform infrared (FTIR) spectroscopy (attenuated total reflectance (ATR), micro-ATR, photoacoustic), gel permeation chromatography, and scanning electron microscopy (SEM). 3. To ascertain the effects of stress and strain state on the rate and mechanisms of PU biodegradation. The effects of in vivo and in vitro static strain (uniaxial and biaxal) as well as in vitro cyclic strain (uniaxial and biaxial) will be examined and the results will be correlated with creep as determined in vitro under oxidative and hydrolytic conditions. 4. To determine the effect of PU surface chemistry, SME's, and the effect of additives (superoxide dismutase (SOD) mimics, N-acetyl-cysteine, and modified dehydroepiandrosterone (DHEA)) on the adhesion of monocytes/macrophages and the formation of foreign body giant cells under static and cyclic strain conditions in vitro. These studies will be correlated with in vivo experiments to examine the effects of antioxidants and macrophage inhibitors on biodegradation.